The objective of this study is to estimate the risk of breast cancer associated with exposures to ambient air pollution, taking into account where women have lived and worked throughout their lives, with a special emphasis on where they were at the time of their first birth. This study uses innovative methods of data linkage and geographic information (GIS) technologies to construct estimates of exposure to selected air contaminants among members of the California Teachers Study (CTS), the largest cohort ever assembled specifically to study breast cancer risk. The specific aims are to: (1.) Characterize the migration history of CTS members within California by constructing profiles of residential and workplace locations over a 30-year time span, including for the critical window of time around first birth; (2.) Characterize potential air pollution exposures associated with residential and workplace location over a 30-year period and, among parous women, at the time of first birth; and (3.) Estimate the risk of breast cancer associated with selected air contaminants associated with residential and workplace locations over a 30-year period, especially for the targeted window of susceptibility around the time of first birth, adjusting for known breast cancer risk factors and sociodemographic characteristics associated with place. The study population will consist of the 118,262 CTS cohort members who were residing in California and did not have a history of breast cancer when they entered the study. Linkage of the cohort to pre-existing vital records, commercially-available address information, and California Department of Education files will be used to construct residential and workplace history profiles for a 30-year time span. Additionally, for parous women, we will use these linkages to identify where subjects worked and lived at the time around their first live birth, as this is thought to be a window of critical susceptibility of breast tissue to environmental insults. A GIS will be used to link the residential and workplace locations to existing air quality databases. Compounds targeted for analysis will include those that have been shown to cause mammary gland tumors in toxicological studies and potential endocrine disruptors. It is anticipated that approximately 4,200 cases of breast cancer will be identified in the CTS in the 15 years since its inception, through linkage to the California Cancer Registry. Breast cancer risk estimates will be calculated for both cumulative exposures and those associated with residential and workplace locations around time of first birth using multivariable Cox models, adjusting for relevant covariates. In studying potential breast cancer risks associated with ambient air pollutants, for which exposures are nearly ubiquitous, this study offers the opportunity to identify an avenue for prevention that could substantially reduce the burden of this disease among future populations of women. PUBLIC HEALTH RELEVANCE: There are at least 35 compounds present in the air we breathe that have been recognized as causing mammary gland tumors in animals. In evaluating potential breast cancer risks associated with these compounds, to which millions of women are exposed, the proposed study offers the opportunity for significant public health impact. Even if relative risks are found to be small, the identification of a risk that is modifiable could lead to substantial reductions in the number of lives lost to this disease.